In the following discussion certain articles and processes will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and processes referenced herein do not constitute prior art under the applicable statutory provisions.
Alcohol poisoning occurs when a patient drinks a very large amount of alcohol (ethanol) during a short period of time. Very large doses of alcohol cause saturation of the enzymes involved in metabolism of alcohol, thus allowing only a fraction of the alcohol to be converted by metabolic transformation to its non-toxic end product (zero-order kinetics for drug metabolism).
Disulfiram (Antabuse™) is a drug that is used to treat both alcohol and cocaine dependencies. Its mechanism of action is inhibition of the enzyme ALDH2 resulting in accumulation of acetaldehyde and symptoms of acetaldehyde poisoning (or alcohol-disulfiram reaction) after consumption of alcohol. Disulfiram was approved for treatment of alcoholism more than 50 years ago, and was initially used as an implant resulting in 100% sobriety. It also caused multiple deaths from alcohol-disulfiram reaction (acetaldehyde poisoning). To avoid deaths and disulfiram toxicity, disulfiram is now administered orally and dose of the drug decreased from 3,000 mg a day to 250 mg a day.
However, this new dosage regime results in reduced overall compliance, as a patient can stop medication and relapse without severe effects. Thus, although current standard of care using oral disulfiram decreases the number of drinking days, it does not ensure abstinence as effectively as an implant (Hughes J C and Cook C C, Addiction 1997 April; 92(4):381-95).
Treatment to reverse the alcohol-disulfiram reaction would allow development of a new generation of long-term disulfiram delivery options without fear of fatalities currently associated with such delivery. The present methods and compositions address this need.